Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX)

Abstract

Purpose: Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. Methods: We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. Results: Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO 2 ≥ 97% (23.5 h [interquartile range (IQR) 8-70] vs. 47 h [IQR 11-93], absolute difference, 23 h; 95% CI 8-38), and more time receiving an FiO 2 of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1-79] vs. 0 h [IQR 0-10], absolute difference, 20 h; 95% CI 14-26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy.

The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design

“…Observational studies and a small, singlecenter RCT suggest that use of a conservative oxygen strategy may be safe and beneficial in pneumonia (60)(61)(62). Some evidence points to improved outcomes with reduced oxygen exposure in several diseases, but recent RCT results are conflicting (63)(64)(65)(66)(67). We intend to implement an oxygenation strategy that compares conservative to liberal oxygenation support, and harmonize with a large scale trial of all-comer ICU patients.…”

Pulmonary infections complicating ARDS

“…While two randomized controlled trials found beneficial effect of avoiding hyperoxia [ 33 , 34 ], a recent large international multicenter trial demonstrated no effect of conservative oxygen therapy in a cohort of critically ill patients [ 35 ]. However, a subsequent sub-study raised the possibility of clinically important harm with conservative oxygen therapy in patients with sepsis [ 36 ].…”

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

“…In randomized trials, "induced" hyperoxia (using 100% oxygen) increased 28-day mortality in septic shock patients [23], while critically ill patients randomized to a target arterial oxygen tension (PaO 2 ) of 70-100 mmHg had lower mortality compared to patients with a "conventional" target of PaO 2 up to 150 mmHg [24] in a single-center study. While a recent large international multicenter trial demonstrated no effect of conservative oxygen therapy in a diverse cohort of critically ill patients [25], a subsequent sub-study raised the possibility of clinically important harm with conservative oxygen therapy in patients with sepsis [26].…”